Ovarian function (encompassing the cyclical production of estrogen and progesterone during the reproductive years and the timing of ovarian failure or menopause) plays an important role in women's health. Menstrual cycle patterns may reflect hormonal status, and specific menstrual characteristics such as cycle length or variability may directly or indirectly affect the risk of developing hormonally-mediated diseases such as osteoporosis. Menopause represents a normal aspect of aging, but it also influences risk for a wide variety of diseases. Studies have reported increased mortality risk with early natural menopause, and age at menopause has been proposed to be a marker of aging and health. The causes and consequences of early menopause is another important focus of this project. Potential endocrine disrupting chemicals are particularly relevant to the mission of NIEHS, and this project work incorporates the study of such exposures. The specific studies that have been completed or are in currently underway within this project include: 1) Menstrual Cycle Patterns in Relation to Risk of Chronic Diseases - analyses using prospectively collected menstrual cycle data from over 800 women followed from their 20's through menopause 2) National Population-Based Studies of Menopausal Status and the Menopausal Transition 3) Pesticide Exposure, Menstrual Cycle Characteristics and Timing of Menopause - analyses using the Agricultural Health Study and a newly-designed longitudinal study using biological measurement of DDE and PCB exposure in relation to timing of natural menopause The first set of studies includes several different analyses using a unique data source, the Menstruation and Reproductive History Study, a longitudinal study of 874 women who prospectively recorded menstrual cycle data for at least five years from their early 20's through their menopause. The specific health conditions examined in relation to menstrual cycle patterns include heart disease, diabetes, perimenopausal fracture risk and total mortality. Increasing menstrual cycle length was associated with peri-menopausal fracture risk, but we saw no relation between cycle length and these other outcomes but increasing bleeding duration was associated with an increased risk of diabetes. The second set of studies include analyses based on the National Health and Nutrition Examination Survey (NHANES) III and the National Health Information Survey (NHIS), including methodologic research comparing different analytic methods for assessing associations with timing of menopause. Results from the NHANES III analyses indicated that hysterectomy with conservation of the ovaries is associated with an earlier age at ovarian failure, as measured by elevated levels of follicle stimulating hormone (FSH). As a comparison of the effect size, the observed association between hysterectomy and elevated FSH is smaller than the association between FSH and current smoking (odds ratio 2.0), a factor that is associated with a 1-2 year decrease in mean age at natural menopause. I will be consulting on an extramurally-funded grant to study the relation between hysterectomy and age at ovarian failure using a prospective study design (Patricia Moorman, Duke University Medical Center, PI). The third set of studies was prompted by the recognition of the endocrine disrupting and ovotoxic potential of specific pesticides. I recently analyzed the relation between plasma DDE and PCB concentrations in a cross-sectional study of timing of natural menopause, and found a strong, dose-response association with DDE and earlier menopause. This finding has led to the development of additional studies focusing on the menstrual cycle and on timing of menopause.